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Competing Interests: We declare no competing interests.

Background: As Rwanda inches closer to the UNAIDS HIV first 95 of knowing one's HIV status by 2030, finding the remaining HIV-positive individuals could be difficult by use of passive methods. Index testing is an approach whereby the exposed contacts of an HIV-positive person are notified and offered an HIV test. We aimed to assess the factors related to the HIV-positive outcome among older people (aged 50 years and above) in Rwanda., Methods: In Rwanda, adults (aged ≥18 years) on antiretroviral therapy (ART) who reported having had sexual partners with unknown HIV status, and individuals with newly diagnosed HIV, described as index cases, were asked to provide details of their sexual partners and invite them to the health facility for HIV testing through client referral, provider referral, or dual referral. We used logistic regression to model the odds of identifying partners who were HIV-positive or aged 50 years or older through partner notification services and to assess predictive factors related to index case and partner, after adjusting for partner related variables (age group, gender, relationship between index and sexual partner, province of residence, notification used) and index case related variables (type of index case, multiple partnership, had unprotected sex in past 12 months, viral load suppression, age difference between notified sexual partner and index case). Written informed consent was obtained from each participant before inclusion in the study. The Rwanda National Ethics Committee approved the protocol for implementation., Findings: Between October, 2018, and September, 2021, 18 453 index cases were recruited and 31 227 partners were notified and tested, of whom 3156 (10·0%) were aged 50 years and older. Of the partners aged 50 years and older, 877 (27·8%) were female and 2279 (88·1%) were male, and 1638 (51·9%) were notified by index cases who were younger than them. Among partners aged 50 years and older, 6·0% (3156) were HIV-positive, with a higher prevalence in partners notified by newly diagnosed index cases 14·7% (46 of 313). In the multivariable analysis, among partners aged 50 years and older, the adjusted odds ratio was 2·66 (95% CI 1·78-3·98) for female partners compared with male partners, 3·14 (2·08-4·77) for partners of newly HIV-diagnosed index cases compared with those of index cases who were already taking ART, and 1·89 (1·07-3·37) for partners who were 15 years older than the index case compared with partners who were 5 years older or younger., Interpretation: Partners of people with newly diagnosed HIV, older individuals who engaged in sexual relationship with younger individuals, and female partners had an increased risk of being diagnosed with HIV. Index testing successfully identified older people with undiagnosed HIV., Funding: None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Selection of optimal second-line antiretroviral therapy (ART) has important clinical and programmatic implications. To inform the 2016 revision of the WHO ART guidelines, we assessed the comparative effectiveness and safety of available second-line ART regimens for adults and adolescents in whom first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens have failed., Methods: In this systematic review and network meta-analysis, we searched for randomised controlled trials and prospective and retrospective cohort studies that evaluated outcomes in treatment-experienced adults living with HIV who switched ART regimen after failure of a WHO-recommended first-line NNRTI-based regimen. We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials for reports published from Jan 1, 1996, to Aug 8, 2016, and searched conference abstracts published from Jan 1, 2014, to Aug 8, 2016. Outcomes of interest were viral suppression, mortality, AIDS-defining illnesses or WHO stage 3-4 disease, discontinuations, discontinuations due to adverse events, and serious adverse events. We assessed comparative efficacy and safety in a network meta-analysis, using Bayesian hierarchical models., Findings: We identified 12 papers pertaining to eight studies, including 4778 participants. The network was centred on ritonavir-boosted lopinavir plus two nucleoside or nucleotide reverse transcriptase inhibitors. Ritonavir-boosted lopinavir monotherapy was the only regimen inferior to others. With the lower estimate of the 95% credible interval (CrI) not exceeding the predefined threshold of 15%, evidence at 48 weeks supported the non-inferiority of ritonavir-boosted lopinavir plus raltegravir to regimens including ritonavir-boosted protease inhibitor plus two NRTIs with respect to viral suppression (odds ratio 1·09, 95% CrI 0·88-1·35). Estimated efficacy of ritonavir-boosted darunavir (800 mg once daily) was too imprecise to determine non-inferiority. Overall, regimens did not differ significantly with respect to continuations, AIDS-defining illnesses or WHO stage 3-4 disease, or mortality., Interpretation: With the exception of ritonavir-boosted lopinavir plus raltegravir, the evidence base is unable to provide strong support to alternative second-line options to ritonavir-boosted protease inhibitor plus two NRTIs, and thus more trials are warranted., Funding: WHO., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: In Rwanda, HIV prevalence among adults aged 15-49 years has been stable at 3% since 2005. The aim of this study was to characterise HIV incidence across Rwanda., Methods: We did a nationally representative, prospective HIV incidence survey for the period of 2013-14, which used two-stage sampling. We randomly selected 492 villages in the first sampling stage and 14 households per village in the second stage. Participants completed a questionnaire and 14 140 people were tested for HIV. 13 728 participants were HIV negative, and were enrolled in the incidence cohort. Participants were retested and surveyed again after 12 months. Weights were calculated as the inverse of the probability to select the villages and the households., Findings: The study period was from Nov 5, 2013, to Nov 15, 2014. Among 14 222 respondents from 6792 households, 14 140 were tested for HIV and 13 728 were HIV negative. Of 12 593 people who participated in the endpoint data collection activities, 5965 (47·4%) were men and the mean age was 30 years (SD 10·8). 11 237 (89·2%) participants lived in rural areas, 4826 (38·3%) were single, and 7140 (56·7%) were married or cohabitating. During the year, 35 participants had seroconversion, including 13 men and 22 women, resulting in an overall incidence of 0·27 per 100 person-years (95% CI 0·18-0·35). Incidence was 0·21 per 100 person-years (0·10-0·32) in men and 0·32 per 100 person-years (0·19-0·45) in women. Our findings suggested multiple breakouts, with multiple seroconversions occurring in three villages and two households. Incidence was higher in adults aged 36-45 years (0·37 per 100 person-years, 0·12-0·62; adjusted hazard ratio [aHR] 4·49, 95% CI 1·30-14·70) relative to those aged 16-25, higher in western province (0·57 per 100 person-years, 0·31-0·87; aHR 5·90, 1·33-25·28) relative to the northern province, and higher in urban areas (0·65 per 100 person-years, 0·23-1·07; aHR 3·10, 1·28-6·99) than in rural areas., Interpretation: The incidence of HIV in Rwanda was higher than that previously estimated from models, with outbreaks seeming to contribute to the ongoing epidemic. Characterisation of incident infections can help the national HIV programmes to plan for preventive interventions tailored to the most at risk populations., Funding: Global Fund to Fight HIV, Tuberculosis and Malaria, WHO Rwanda, UNAIDS Rwanda, and the Government of Rwanda., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: New antiretroviral therapy (ART) regimens for HIV could improve clinical outcomes for patients. To inform global guidelines, we aimed to assess the comparative effectiveness of recommended ART regimens for HIV in ART-naive patients., Methods: For this systematic review and network meta-analysis, we searched for randomised clinical trials published up to July 5, 2015, comparing recommended antiretroviral regimens in treatment-naive adults and adolescents (aged 12 years or older) with HIV. We extracted data on trial and patient characteristics, and the following primary outcomes: viral suppression, mortality, AIDS defining illnesses, discontinuations, discontinuations due to adverse events, and serious adverse events. We synthesised data using network meta-analyses in a Bayesian framework and included older treatments, such as indinavir, to serve as connecting nodes. We defined network nodes in terms of specific antivirals rather than specific ART regimens. We categorised backbone regimens and adjusted for them through group-specific meta-regression. We used the GRADE framework to interpret the strength of inference., Findings: We identified 5865 citations through database searches and other sources, of which, 126 articles related to 71 unique trials were included in the network analysis, including 34 032 patients randomly assigned to 161 treatment groups. For viral suppression at 48 weeks, compared with efavirenz, the odds ratio (OR) for viral suppression was 1·87 (95% credible interval [CrI] 1·34-2·64) with dolutegravir and 1·40 (1·02-1·96) with raltegravir; with respect to viral suppression, low-dose efavirenz was similar to all other treatments. Both low-dose efavirenz and integrase strand transfer inhibitors tended to be protective of discontinuations due to adverse events relative to normal-dose efavirenz. The most protective effect relative to efavirenz in network meta-analyses was that of dolutegravir (OR 0·26, 95% CrI 0·14-0·47), followed by low-dose efavirenz (0·39, 0·16-0·92). Owing to insufficient data, we could make no conclusions about serious adverse events. Low event rates also limited the quality of evidence with regard to mortality and AIDS defining illnesses., Interpretation: The efficacy and safety of ART has substantially improved with the introduction of newer drug classes of antiretrovirals that are now available to patients and HIV care providers. Their improved tolerance could be part of a larger solution to improve retention, which is a challenge, particularly in low-income and middle-income country settings., Funding: The World Health Organization., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Morbidity associated with HIV infection is poorly characterised, so we aimed to investigate the contribution of different comorbidities to hospital admission and in-hospital mortality in adults and children living with HIV worldwide., Methods: Using a broad search strategy combining terms for hospital admission and HIV infection, we searched MEDLINE via PubMed, Embase, Web of Science, LILACS, AIM, IMEMR and WPIMR from inception to Jan 31, 2015, to identify studies reporting cause of hospital admission in people living with HIV. We focused on data reported after 2007, the period in which access to antiretroviral therapy started to become widespread. We estimated pooled proportions of hospital admissions and deaths per disease category by use of random-effects models. We stratified data by geographical region and age., Findings: We obtained data from 106 cohorts, with reported causes of hospital admission for 313 006 adults and 6182 children living with HIV. For adults, AIDS-related illnesses (25 119 patients, 46%, 95% CI 40-53) and bacterial infections (14 034 patients, 31%, 20-42) were the leading causes of hospital admission. These two categories were the most common causes of hospital admission for adults in all geographical regions and the most common causes of mortality. Common region-specific causes of hospital admission included malnutrition and wasting, parasitic infections, and haematological disorders in the Africa region; respiratory disease, psychiatric disorders, renal disorders, cardiovascular disorders, and liver disease in Europe; haematological disorders in North America; and respiratory, neurological, digestive and liver-related conditions, viral infections, and drug toxicity in South and Central America. For children, AIDS-related illnesses (783 patients, 27%, 95% CI 19-34) and bacterial infections (1190 patients, 41%, 26-56) were the leading causes of hospital admission, followed by malnutrition and wasting, haematological disorders, and, in the African region, malaria. Mortality in individuals admitted to hospital was 20% (95% CI 18-23, 12 902 deaths) for adults and 14% (10-19, 643 deaths) for children., Interpretation: This review shows the importance of prompt HIV diagnosis and treatment, and the need to reinforce existing recommendations to provide chemoprophylaxis and vaccination against major preventable infectious diseases to people living with HIV to reduce serious AIDS and non-AIDS morbidity., Funding: None., (Copyright © 2015 World Health Organization. Published by Elsevier Ltd/Inc/BV. All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Background: Continued debate exists about whether initiation of antiretroviral therapy (ART) in symptom-free patients at higher baseline CD4 cell counts results in important clinical benefits. We aimed to examine to what extent baseline CD4 cell count at linkage to HIV care and at ART initiation predicts mortality in adults with HIV in Rwanda., Methods: We included data for patients with HIV in Rwanda who were aged 15 years or older and linked to care or initiated ART between Jan 1, 1997, and April 30, 2014, from nationally representative databases. We analysed the effect on mortality of baseline CD4 cell count at ART initiation and at linkage to care. Follow-up time was measured from time of ART initiation and from linkage to HIV care to study exit. To account for effect modification by time, we stratified by era of linkage (before 2008 vs 2008 or after) and for other indications for initiation of ART. We also stratified CD4 cell count by indication to initiate ART other than CD4 cell count status. We used Cox proportional hazard regressions to examine the effect of CD4 cell count at linkage and at ART initiation on mortality., Findings: Our analysis was based on data from 50,147 patients who initiated ART and 72,061 patients linked to care. In the late era (2008 and after), linkage to care at a CD4 cell count of 100-199 cells per μL without any further indication was associated with higher mortality than linkage at 200-349 cells per μL (hazard ratio [HR] 1·37, 95% CI 0·95-1·97); the effect was much the same for initiation of ART in this CD4 stratum (1·37, 0·92-2·04). For higher CD4 strata, linkage to care at 500 cells per μL or more was protective (0·53, 0·39-0·72), whereas the reported effect of initiation of ART on mortality was not distinguishable from chance alone (0·82, 0·21-3·20)., Interpretation: Efforts are needed to link and retain patients early in pre-ART HIV care. In settings where ART is not yet available for immediate treatment, retention in a strong pre-ART programme is effective at improving survival., Funding: The Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Rwanda has made remarkable progress towards HIV care programme with strong national monitoring and surveillance. Knowledge about the HIV care continuum model can help to improve outcomes in patients. We aimed to quantify engagement, mortality, and loss to follow-up of patients along the HIV care continuum in Rwanda in 2013., Methods: We collated data for individuals with HIV who participated in the national HIV care programme in Rwanda and calculated the numbers of individuals or proportions of the population at each stage and the transition probabilities between stages of the continuum. We calculated factors associated with mortality and loss to follow-up by fitting Cox proportional hazards regression models, one for the stage of care before antiretroviral therapy (ART) initiation and another for stage of care during ART., Findings: An estimated 204,899 individuals were HIV-positive in Rwanda in 2013. Among these individuals, 176,174 (86%) were in pre-ART or in ART stages and 129,405 (63%) had initiated ART by the end of 2013. 82·1% (95% CI 80·7-83·4) of patients with viral load measurements (n=3066) were virally suppressed (translating to 106,371 individuals or 52% of HIV-positive individuals). Mortality was 0·6% (304 patients) in the pre-ART stage and 1·0% (1255 patients) in the ART stage; 2247 (3·9%) patients were lost to follow-up in pre-ART stage and 2847 (2·2%) lost in ART stage. Risk factors for mortality among patients in both pre-ART and ART stages included older age, CD4 cell count at initiation, and male sex. Risk factors for loss to follow-up among patients at both pre-ART and ART stages included younger age (age 10-29 year) and male sex., Interpretation: The HIV care continuum is a multitrajectory pathway in which patients have many opportunities to leave and re-engage in care. Knowledge about the points at which individuals are most likely to leave care could improve large-scale delivery of HIV programmes., Funding: The Bill & Melinda Gates Foundation., (Copyright © 2015 Elsevier Ltd. All rights reserved.)